Functional and morphological changes in the hippocampal neuronal circuits associated with epileptic seizures

Abstract

Purpose: We review what is currently known about functional and morphologic plasticity of hippocampal neuronal circuits in animal epilepsy models. Results: Perforant-path kindling has been shown to enhance excitatory synaptic transmission in the dentate gyms significantly, and this enhancement has lasted for ≥1 month after kindling. However, in our rapid kindling experiment with an interstimulus interval of 5 min, perforant-path kindling resulted in behavioral convulsions and prolonged the afterdischarge duration, but dentate synaptic transmission remained depressed during kindling. Conclusions: These results indicate that kindling-induced synaptic potentiation is not necessary for kindling development. Conversely, epileptic seizures have led to the anomalous sprouting of mossy fibers, a process thought to induce hyper-excitation of granule cells. We conclude that the sprouting of mossy fibers did not play a critical role in kindling, because we observed no significant correlation between the mossy fiber sprouting and kindling development. Epileptic seizures also have been shown to increase γ-aminobutyric acid (GABA)A receptor-mediated inhibition during interictal periods. Although this strengthening of GABAergic inhibition is likely to be a defensive measure against seizure initiation, some studies have suggested that another type of GABAergic response facilitates seizure activity. The possibility of GABAA receptor-mediated excitation during ictal periods is theoretically examined.